The present invention relates to a mass spectrometer and a method of mass spectrometry.
A known mass spectrometer comprises a Matrix Assisted Laser Desorption Ionisation (“MALDI”) ion source coupled to an orthogonal acceleration Time of Flight mass analyser. Ions are orthogonally accelerated in the mass analyser and the time of flight of the ions is measured. This enables the mass to charge ratio of the ions to be determined. Orthogonal acceleration Time of Flight mass analysers are particularly advantageous compared to axial or in-line Time of Flight mass analysers when coupled to a MALDI ion source in that the resolution, mass calibration and mass accuracy of an orthogonal acceleration Time of Flight mass analyser is substantially unaffected by variations in ion desorption velocities from the MALDI ion source.
A further advantage of using an orthogonal acceleration Time of Flight mass analyser in combination with a MALDI ion source is that variations in the sample thickness or the surface potential applied to the MALDI target plate do not directly affect the subsequent time of flight of ions in the flight or drift region of the orthogonal acceleration Time of Flight mass analyser.
Two different types of instrument are known. The first type of instrument utilises a radio frequency collisional cooling gas cell that lowers the axial and orthogonal kinetic energy of the ions to levels appropriate for the orthogonal acceleration Time of Flight mass analyser. These instruments are more complex, more expensive, and less efficient compared to in-line or axial MALDI mass spectrometers comprising a Time of Flight mass analyser. The cooling gas may promote matrix cluster formation that increases chemical background and reduces signal to noise. The second type of instrument does not employ gaseous collisional damping and as such the higher precursor ion kinetic energies permit the recording of high energy collision induced dissociation (CID) MS/MS fragmentation mass spectra. Ions are allowed to retain their axial velocities and the detector of the orthogonal acceleration Time of Flight mass analyser has to be larger in order to cope with the larger angular spread of ions caused by the large axial energy spread. One example of the second type of instrument is a hybrid magnetic sector orthogonal acceleration Time of Flight tandem MS/MS instrument (Bateman et al., Rapid Commun. Mass Spectrom. 9 (1995) 1227). The instrument comprises a MALDI ion source, a magnetic sector mass filter for high resolution selection of precursor ions, a collision induced dissociation (CID) gas cell and an orthogonal acceleration Time of Flight mass analyser for recording the fragment or daughter ions generated in the gas cell.
In this instrument fragment or daughter ions retain the original parent or precursor ion velocity, as such, their kinetic energy is proportional to their mass. When a parent or precursor ion and its associated fragment or daughter ions reach the orthogonal acceleration Time of Flight mass analyser the ions are accelerated through a constant electric field from the pusher region into the orthogonal acceleration Time of Flight flight tube.
Conventional mass spectrometers of the second type of instrument described above which comprise a MALDI ion source coupled to an orthogonal acceleration Time of Flight mass analyser suffer from the problem that ions arriving at the orthogonal acceleration region of the mass analyser will have a wide range of axial energies. Accordingly, when the ions are orthogonally accelerated the ion detector is only able to detect and record ions having a relatively narrow or small range of mass or mass to charge ratios. Since the orthogonal flight or path length of ions in the mass analyser is limited and since the ion detector is constrained in size then these factors (as will be discussed in more detail below) place a limitation on the range of mass or mass to charge ratios of ions which can both be orthogonally accelerated and also subsequently detected by the ion detector of the mass analyser.
It is therefore desired to provide an improved mass spectrometer and an improved method of mass spectrometry.